Neuroprotective effect of selective hypothermic cerebral perfusion in extracorporeal cardiopulmonary resuscitation: A preclinical study

Kerong Zhai; Mingming Li; Jian Li; Shilin Wei; Zhenzhen Li; Yanchun Zhang; Bingren Gao; Xiangyang Wu; Yongnan Li

doi:10.1016/j.xjon.2022.07.007

Neuroprotective effect of selective hypothermic cerebral perfusion in extracorporeal cardiopulmonary resuscitation: A preclinical study

JTCVS Open. 2022 Aug 3:12:221-233. doi: 10.1016/j.xjon.2022.07.007. eCollection 2022 Dec.

Authors

Kerong Zhai^{1

2}, Mingming Li^{2

3}, Jian Li², Shilin Wei^{1

2}, Zhenzhen Li⁴, Yanchun Zhang¹, Bingren Gao¹, Xiangyang Wu¹, Yongnan Li^{1

2}

Affiliations

¹ Department of Cardiac Surgery, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China.
² Department of Laboratory of Extracorporeal Life Support, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China.
³ Department of Neurology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China.
⁴ Department of Cardiopulmonary Bypass, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China.

Abstract

Objective: Neurologic complications seriously affect the survival rate and quality of life in patients with extracorporeal cardiopulmonary resuscitation (ECPR) undergoing cardiac arrest. This study aimed to repurpose selective hypothermic cerebral perfusion (SHCP) as a novel approach to protect the brains of these patients.

Methods: Rats were randomly allocated to Sham, ECPR, and SHCP combined ECPR (CP-ECPR) groups. In the ECPR group, circulatory resuscitation was performed at 6 minutes after asphyxial cardiac arrest by extracorporeal membrane oxygenation. The vital signs were monitored for 3 hours, and body and brain temperatures were maintained at the normal level. In the CP-ECPR group, the right carotid artery catheterization serving as cerebral perfusion was connected with the extracorporeal membrane oxygenation device to achieve selective brain cooling (26-28 °C). Serum markers of brain injury and pathomorphologic changes in the hippocampus were evaluated. Three biological replicates further received RNA sequencing in ECPR and CP-ECPR groups. Microglia activation and inflammatory cytokines in brain tissues and serum were detected.

Results: SHCP rapidly reduced the brain-targeted temperature and significantly alleviated nerve injury. This was evident from the reduced brain injury serum biomarker levels, lower pathologic scores, and more surviving neurons in the hippocampus in the CP-ECPR group. Furthermore, more differentially expressed genes for inflammatory responses were clustered functionally according to Kyoto Encyclopedia of Genes and Genomes pathway analysis. And SHCP reduced microglia activation and the release of proinflammatory mediators.

Conclusions: Our preliminary data indicate that SHCP may serve as a potential therapy to attenuate brain injury via downregulation of neuroinflammation in patients with ECPR.

Keywords: CA, cardiac arrest; DEGs, differentially expressed genes; ECMO, extracorporeal membrane oxygenation; ECPR, extracorporeal cardiopulmonary resuscitation; H&E, hematoxylin–eosin; ICAM-1, Intercellular adhesion molecule-1; IHC, immunohistochemistry; IL-1β/6/8, interleukin-1β/6/8; Iba1, ionized calcium-binding adaptor molecule 1; MAP, mean arterial pressure; NSE, neuron-specific enolase; PCR, polymerase chain reaction; RNA-seq, RNA sequencing; S100β, S-100β protein; SHCP, selective hypothermic cerebral perfusion; TNF-α, tumor necrosis factor-α; UCH-L1, ubiquitin C-terminal hydrolase-L1; cardiac arrest; cerebral protection; extracorporeal cardiopulmonary resuscitation; hypothermic cerebral perfusion; neuroinflammation.